Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics,thrombin and thermolysin inhibitors

Summary A relative comparison of the binding properties of different drug molecules requires their mutual superposition with respect to various alignment criteria. In order to validate the results of different alignment methods, the crystallographically observed binding geometries of ligands in the pocket of a common protein receptor have been used. The alignment function in the program SEAL that calculates the mutual superposition of molecules has been optimized with respect to these references. Across the reference data set, alignments could be produced that show mean rms deviations of approximately 1 Å compared to the experimental situation. For structures with obvious skeletal similarities a multiple-flexible fit, linking common pharmacophoric groups by virtual springs, has been incorporated into the molecular mechanics program MOMO. In order to combine conformational searching with comparative alignments, the optimized SEAL approach has been applied to sets of conformers generated by MIMUMBA, a program for conformational analysis. Multiple-flexible fits have been calculated for inhibitors of ergosterol biosynthesis. Sets of different thrombin and thermolysin inhibitors have been conformationally analyzed and subsequently aligned by a combined MIMUMBA/SEAL approach. Since for these examples crystallographic data on their mutual alignment are available, an objective assessment of the computed results could be performed. Among the generated conformers, one geometry could be selected for the thrombin and thermolysin inhibitors that approached reasonably well the experimentally observed alignment.     

氮原子在Ni平坦和缺陷表面上的吸附和振动

 构造了氮－镍相互作用的5－参数Morse势，研究了氮原子在Ni（\r\n100），Ni（110）和Ni（111）平坦表面的吸附和振动，获得了氮原子\r\n在三个低指数表面的吸附位、吸附构型、结合能和本征振动等数据，计\r\n算结果与实验结果非常吻合．同时，与Ni（100）表面对比，系统研究\r\n了氮原子在Ni（510）台阶面的吸附和扩散．计算结果表明，氮原子在\r\n台阶下部形成最稳定的吸附态，台阶对下台面上扩散的氮原子形成捕获\r\n势，对上台面上扩散的氮原子形成反射势．     

离聚体的结构表征 Ⅲ.EXAFS法测定含氟的铜离聚体的精细结构

本文报道了用先进的EXAFS及ESR等方法研究了羧酸型含氟的铜(Ⅱ)离聚体离子微区的内部精细结构,结果表明,铜离聚体的离子微区主要由羧酸根桥键的双核配位结构单元及平面四方形的配位结构单元等聚集而成。在双核配位结构单元中第一层为Cu~(2+)—O配位,配位数为4,配位键键长为1.96A,第二配位层为Gu~(2+)—Cu~(2+)配位,Cu~(2+)—Gu~(2+)间距为2.64A。平面四方形的配位结构单元Cu~(2+)—O的配位数为4,配位键键长为1.96A。共聚物中羧基含量对离聚体的基本配位结构单元和离子微区的精细结构影响较小,但对微区大小有影响。     

铌酸锂晶体性能的组成依赖性(英文)

总结了铌酸锂晶体的各项性能指标,显示了其对晶体实际组成的强烈依赖性.利用化学键模型定量地解释了这种依赖性产生的根源,从而说明了制约该晶体性能提高的关键因素是晶体结构中的缺陷控制.     

Synthesis, structural determination and photo-antiproliferative activity of new 3-pyrazolyl or -isoxazolyl substituted 4-hydroxy-2(1H)-quinolinones

A convenient route to new 3-quinolinonyl-pyrazoles and isoxazoles is described through cyclization of 3-[(E)-3-(dimethylamino)-2-propenoyl]-4-hydroxy-1-methyl-2(1H)-quinolinone. The phototoxicity as well as the cytotoxic activities of the title compounds are evaluated against leukemia- and adenocarcinoma-derived cell lines in comparison to the normal human keratinocytes.     

Structural optimization with parameter-transfer finite element

A mathematical method to solve structural problems, using parameter-transfer finite elements (P-TFE) was recently proposed by the authors [1] [2] [3]. The proposed transfer finite element approach is able to create a mathematical model of a structure, taking into account directly the whole behaviour of the structure under dynamic, aerodynamic, and thermal actions, and not by assembling, in a separate fashion, the stiffness and the mass matrix on one side and the external load vector as performed by the classical finite element procedure.The purpose of this paper is to apply the above methodology to optimization problems, in particular to obtain the minimum structural weight for a beam, under primary constraints on buckling load or natural frequencies.The use of P-TFE in the field of structural optimization overcomes most difficulties of the usual techniques of solution and the element is particularly useful in the evaluation of the sensitivity matrix.The formulation of the optimization problem based on P-TFE is presented and some applications are studied. The numerical results obtained are compared with other existing methodologies and briefly discussed.

---

Sommario Gli autori hanno già proposto un metodo per studiare problemi strutturali [1] [2] [3], introducendo una nuova metodologia di discretizzazione, basata sull'impiego di elementi finiti di trasferimento, funzioni esplicite di un parametro, indicati come P-TFE. Tali elementi sono in grado di rappresentare, in similitudine alla funzione di trasferimento, il comportamento completo dell'elemento strutturale in esame, soggetto ad azioni dinamiche, aerodinamiche e termiche; sono parimenti in grado di produrre, in similitudine al metodo degli elementi finiti, un modello matematico discreto di un continuo.Scopo del presente lavoro è di applicare detta metodologia a problemi di ottimizzazione, in particolare alla ricerca del minimo peso per una trave che mantenga inalterate le sue caratteristiche di carico critico o le frequenze naturali di vibrazione.Vengono quindi presentati alcuni risultati numerici dei casi esaminati e confrontati con quelli ottenuti da altri autori con l'impiego di altre metodologie.

---

List of Symbols {B} _m vector of the generalized state variables - {C} _m vector of integration constants - [I] unit matrix - EI bending stiffness - A cross-sectional area - u adimensional thickness - l beam length - M,M bending moment - [N] _m shape function ofm-th order - [N*] shape function atx ₀ - P axial load - [R] _i transfer matrix of thei-th element - T,T shear force - w transverse displacement - x adimensional independent variable - x ₀ value ofx at the left of the element - {Y} vector of state variables - {Y*} imposed condition atx ₀ - _0m Kronecker delta with the first pedix always set equal to zero - normalized eigenfrequency - normalized buckling load - mass density     

Classifying Structural Characteristics to Enhance Computation of Enthalpy of Formation of Halohydrocarbons

Density functional theory (DFT) calculations are made and least squares calibration performed for various halohydrocabons, which were 27 straight‐chain alkyl halides, 20 branch‐chain alkyl halides and 19 aromatic halides, to determine their enthalpies of formation (ΔH_f). The mean absolute error (M. |A.E.|) in ΔH_f across 66 molecular computations was only 7.8 kJ/mol (1.9 kcal/mol). Grouping the molecules by their structural characteristics improved M. |A.E.| of ΔH_f by 0.2–2.2 kJ/mol over that obtained using corresponding modified data for the same 66 unclassified molecules.     

硼烷结构规则的量子化学计算

利用EHMO方法,对n=5～12的完整多面体硼烷骨架、缺一个和两个顶点以及戴一个和两个帽原子的各种异构体进行了量子化学计算。直接对硼烷的价成键轨道数公式BMO=4n-[f+3(s+1)]进行了验证。在对计算结果讨论的基础上,进一步探讨了骨架几何结构与成键轨道数之间的关系。     

Electron and light microscopical investigation of defect structures in mesophases of pharmaceutical substances

 Transmission electron microscopy of freeze fractured and replicated samples (TEM) and polarizing light microscopy (PLM) are used to investigate the defect structures of the thermotropic and lyotropic mesophases of the non-steroidal antiinflammatory drug fenoprofen sodium and of the thermotropic mesophase of the nonionic surfactant sucrose oleate (O1570). All mesophases have a layered, smectic structure. The thermotropic liquid crystal of feno-profen sodium is an interdigitated smectic A phase (smectic Ad) having the highest viscosity of the investigated samples. The thermotropic mesophase of the sugar ester is also of the type smectic A, likely to be of subtype smectic A2 (bilayered smectic structure). The lyotropic mesophase is of lamellar liquid crystalline nature and has a much lower viscosity than the thermotropic mesophases. In the PLM the lyotropic fenoprofen mesophase has a strong tendency to form a pseudoisotropic texture, indicating a strong tendency to form undisturbed layered structures. Other textures exhibited in the PLM are fan-shaped texture and maltese-cross texture. Confocal domains, cylinders, pits and peaks as well as screw dislocations are found in great number in the TEM. However, no greater regions of undisturbed lamellar arrangement in the lyotropic mesophase could be detected. The only texture of the thermotropic fenoprofen mesophase visible in the PLM is the fan-shaped texture, indicating confocal domains as predominant structural elements. However, no confocal domains (tori or Dupin cyclides) are found in the TEM. In the PLM the sugar–ester mesophase exhibited a fan-shaped texture, maltese crosses and oily streaks as dominant textures. In the TEM only a few +π and −π disclinations and imperfect confocal domains could be detected. The discrepancies in the appearance of defect structures and textures between the mesophases as well as the discrepancies in the findings in the PLM and in the TEM investigations are caused by the different sample preparation and the different viscosities of the mesophases. Received: 28 May 1997 Accepted: 2 September 1997